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Progress in Paralyzed Rats Using Embryonic Stem Cells

Researchers have partially restored function in paralyzed animals by enticing transplants of embryonic stem cell-derived neurons (nerve cells) in the spinal cord to connect with muscles. If future studies go well, similar techniques may one day be used to treat human disorders such as spinal cord injury and amyotrophic lateral sclerosis (ALS).

Dr. Douglas Kerr of The Johns Hopkins University School of Medicine and his
colleagues, in work funded partly by NIH’s National Institute of Neurological
Disorders and Stroke (NINDS), cultured embryonic stem cells from mice with chemicals
that caused them to grow into motor neurons, the nerve cells that send signals
to muscle telling them to move. Just before transplantation, they added nerve
growth factors to the culture. Most of the cells were also cultured with a substance
that helps growing nerve fibers (called axons) overcome chemicals produced by
myelin, the insulation around nerve fibers in the spinal cord, that normally
inhibit their growth.

The cells were transplanted into eight groups of paralyzed rats. Each group
received a different combination of treatments. Some received injections of a
drug called rolipram, which is approved to treat depression and also helps counteract
axon-inhibiting signals from myelin. Some also received transplants of neural
stem cells that secreted a nerve growth factor that causes axons to grow toward
it (called GDNF) into the sciatic nerve.

Three months after the transplants, the rats that had received the full cocktail
of treatments had several hundred transplant-derived axons extending into the
nervous system, more than in any other group. The axons in these animals reached
all the way down the sciatic nerve to form functional connections with muscle
in the lower leg. The rats showed an increase in the number of functioning motor
neurons and an approximately 50% improvement in hind limb grip strength by 4
months after transplantation. In contrast, none of the rats given other combinations
of treatments recovered lost function.

Follow-up experiments with GDNF treatment on only one side of the body showed
that, by 6 months after treatment, 75% of rats given the full combination of
treatments regained the ability to bear weight on the GDNF-treated limbs and
to take steps and push away with the foot on that side of the body.

This study is the first to show that transplanted motor neurons can form functional
connections with the adult mammalian nervous system. Much work remains to be
done before a similar strategy could be tried in humans, however. “This study
provides a 'recipe' for using stem cells to reconnect the nervous system,” Dr.
Kerr says. "It raises the notion that we can eventually achieve this in humans,
although we have a long way to go."